Kisspeptin-54 Accurately Identifies Hypothalamic Gonadotropin-Releasing Hormone Neuronal Dysfunction in Men with Congenital Hypogonadotropic Hypogonadism.

BACKGROUND: Hypogonadotropic hypogonadism (HH) is hypogonadism due to either hypothalamic or pituitary dysfunction. While gonadotropin-releasing hormone (GnRH) can directly test pituitary function, no specific test of hypothalamic function exists. Kisspeptin-54 (KP54) is a neuropeptide that directly stimulates hypothalamic GnRH release and thus could be used to specifically interrogate hypothalamic function. Congenital HH (CHH) is typically due to variants in genes that control hypothalamic GnRH neuronal migration or function. Thus, we investigated whether KP54 could accurately identify hypothalamic dysfunction in men with CHH. METHODS: Men with CHH (n = 21) and healthy eugonadal men (n = 21) received an intravenous bolus of either GnRH (100 µg) or KP54 (6.4 nmol/kg), on 2 occasions, and were monitored for 6 h after administration of each neuropeptide. RESULTS: Maximal luteinizing hormone (LH) rise after KP54 was significantly greater in healthy men (12.5 iU/L) than in men with CHH (0.4 iU/L; p < 0.0001). KP54 more accurately differentiated CHH men from healthy men than GnRH (area under receiver operating characteristic curve KP54: 1.0, 95% CI 1.0-1.0; GnRH: 0.88, 95% CI 0.76-0.99). Indeed, all CHH men had an LH rise <2.0 iU/L following KP54, whereas all healthy men had an LH rise >4.0 iU/L. Anosmic men with CHH (i.e., Kallmann syndrome) had even lower LH rises after KP54 than did normosmic men with CHH (p = 0.017). Likewise, men identified to have pathogenic/likely pathogenic variants in CHH genes had even lower LH rises after KP54 than other men with CHH (p = 0.035). CONCLUSION: KP54 fully discriminated men with CHH from healthy men. Thus, KP54 could be used to specifically interrogate hypothalamic GnRH neuronal function in patients with CHH.

One hundred eighteen days on a ventilator: a COVID-19 success story against all odds.

Emerging data suggest that patients with certain comorbidities requiring intensive care unit (ICU) admission for COVID-19 have a poor prognosis. This report describes a case of a patient with multiple comorbidities who contracted COVID-19 pneumonitis but was successfully weaned off invasive mechanical ventilation after 118 days, despite his admission being complicated by recurrent septic episodes and requirement for advanced cardiovascular support and renal replacement therapy. Of note, our patient received three courses of steroids in total during his ICU stay,and current literature strongly supports the use of steroids in critically unwell patients with COVID-19. To the best of our knowledge, this is the longest reported ventilated time and intensive care/hospital stay for a surviving patient with COVID-19 and highlights the importance of allowing sufficient time for clinical interventions to take effect, even when the prognosis appears bleak.

ARE ANTIBIOTICS OF ANY USE IN THE MANAGEMENT OF GRANULOMA ANNULARE IN CHILDREN?

BACKGROUND: Granuloma annulare (GA) is a benign inflammatory dermatosis of unknown cause, of which generalised granuloma annulare (GGA) is a subtype that tends to be resistant to treatment. Various antibiotics have been used to treat GGA, the most recent being combination therapy with rifampicin, ofloxacin and minocycline (ROM). This study aims to explore the efficacy of antibiotics in treating GGA, and whether antibiotics may be useful in children with GGA. MATERIALS AND METHODS: A systematic review of literature published from 1947 to 2017 was undertaken in order to evaluate the use of antibiotics in treating GGA. Data on characteristics of children with GGA were extracted and eligible studies were then qualitatively analysed. RESULTS: Seven hundred and ninety (790) potential studies were identified, of which 16 were eligible for inclusion in the final analysis. Of these 16 studies, majority were case studies (n=9, 56.3%), with 2 case series (12.5%), 2 retrospective studies (12.5%) and 3 open-label prospective studies (18.8%). Main antibiotic treatments reported were either monthly combination therapy of rifampicin, ofloxacin and minocycline (ROM), or monotherapy with dapsone or doxycycline. Out of a total of 158 patients with GA, 72 patients (45.6%) were treated with antibiotics. Of the 72, 48.6% (n=35) of these patients had GGA while 4 were children; two with GA (2 with GGA), all of whom were treated with dapsone. CONCLUSION: There is paucity of evidence to support the use of antibiotics in the treatment of GGA in children. Although ROM has shown promising results in adults, more studies are needed to validate these findings in children.

FSH Requirements for Follicle Growth During Controlled Ovarian Stimulation.

Introduction: Ovarian follicle growth is a key step in the success of assisted reproductive treatment, but limited data exists to directly relate follicle growth to recombinant FSH (rFSH) dose. In this study, we aim to evaluate FSH requirements for follicular growth during controlled ovarian stimulation. Method: Single center retrospective cohort study of 1,034 IVF cycles conducted between January 2012-January 2016 at Hammersmith Hospital IVF unit, London, UK. Median follicle size after 5 days of stimulation with rFSH and the proportion of antral follicles recruited were analyzed in women treated with rFSH alone to induce follicular growth during IVF treatment. Results: Starting rFSH dose adjusted for body weight (iU/kg) predicted serum FSH level after 5 days of rFSH (r 2 = 0.352, p < 0.0001), median follicle size after 5 days of rFSH, and the proportion of antral follicles recruited by the end of stimulation. Day 5 median follicle size predicted median follicle size on subsequent ultrasound scans (r 2 = 0.58-0.62; p < 0.0001), and hence time to oocyte maturation trigger (r 2 = 0.22, P < 0.0001). Insufficient rFSH starting dose that required >5% dose-increase was associated with increased variability in follicle size on the day of oocyte maturation trigger, and negatively impacted the number of mature oocytes retrieved. Conclusion: Weight-adjusted rFSH dose correlates with follicular growth during ovarian stimulation. Early recruitment of follicles using a sufficient dose of rFSH from the start of stimulation was associated with reduced variability in follicle size at time of oocyte maturation trigger and an increased number of mature oocytes retrieved.

Evolution of HIV-Associated Lymphoma Over 3 Decades.

INTRODUCTION: The emergence of combined antiretroviral therapy (cART) and improvements in the management of opportunistic infections have altered the HIV epidemic over the last 30 years. We aimed to assess changes to the biology and outcomes of HIV-associated lymphomas over this period at the national center for HIV oncology in the United Kingdom. METHODS: Clinical characteristics at lymphoma diagnosis have been prospectively collected since 1986, along with details of lymphoma treatment and outcomes. The clinical features and outcomes were compared between 3 decades: pre-cART decade (1986-1995), early-cART decade (1996-2005), and late-cART decade (2006-2015). RESULTS: A total of 615 patients with HIV-associated lymphoma were included in the study: 158 patients in the pre-cART era, 200 patients in the early-cART era, and 257 patients in the late-cART era. In more recent decades, patients were older (P < 0.0001) and had higher CD4 cell counts (P < 0.0001) at lymphoma diagnosis. Over time, there has also been a shift in lymphoma histological subtypes, with an increase in lymphoma subtypes associated with moderate immunosuppression. The overall survival for patients with HIV-associated lymphoma has dramatically improved over the 3 decades (P < 0.0001). CONCLUSION: Over the last 30 years, the clinical demographic of HIV-associated lymphomas has evolved, and the outcomes have improved.